FDG and FDOPA PET Demonstration of Functional Brain Abnormalities

Early Phase 1

• Conditions: Glioblastoma
• Interventions: Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Multiparametric Magnetic Resonance Imaging Scan; Radiation: Fludeoxyglucose F-18; Radiation: fluorine F 18 fluorodopa

• Registration Number: NCT04315584
• Lead Sponsor: University of Virginia

Brief Summary

The purpose of this pilot study will be to conduct a clinical trial using a time-of-flight PET scanner and MRI scanner to test an improved method for differentiating tumor recurrence from radiation necrosis in glioblastoma patients. We will attempt to do so by performing a static and dynamic FDG-PET scan, a static and dynamic FDOPA-PET scan, and a multiparametric MRI scan - then comparing the results with surgical pathology and static FDG-PET scans. We hypothesize that the new quantitative kinetic analytical methods using FDOPA in combination with FDG will provide crucial functional information to distinguish recurrent tumors from treatment-induced radiation changes in patients with treated brain neoplasms. This is important for improving patient outcomes by allowing treating physicians to more accurately tailor treatments. Furthermore, dynamic FDG and FDOPA PET will be combined with high resolution anatomic and physiologic MRI in order to develop a multimodal multiparametric approach for differentiating tumor recurrence from treatment effect.

Detailed Description

PRIMARY OBJECTIVES:

I. The primary objective will be to evaluate the diagnostic accuracy of Dynamic PET imaging in differentiating tumor recurrence from treatment effect (radiation necrosis or pseudoprogression) in patients previously treated with chemo-radiation therapy for primary high grade gliomas. This will be accomplished by examining the concordance between the Dynamic PET imaging prediction and the criterion standard, which will be based on either surgical pathology or an integrated clinical/MRI determination within a 3-6 month interval after Dynamic PET imaging.

SECONDARY OBJECTIVES:

I. The diagnostic accuracy of Static PET imaging, advanced MRI, and advanced MRI + Dynamic PET imaging in differentiating tumor recurrence from radiation-induced necrosis in high grade glioma patients will be examined in the same exact way as just outlined for Dynamic PET imaging.

OUTLINE:

Subjects receive 18FDG (first scan) and (18)F-FDOPA (2-14 days from the first scan) intravenously (IV) slowly over a period of 15-20 seconds and then undergo dynamic PET scans over a period of 60-90 minutes. CT scans on the subjects are performed before the dynamic PET scans for 5 minutes. Subjects also undergo MRI brain examinations just prior to the FDOPA scan over a period of 1 hour, which includes T1 weighed, T1 weighted contrast enhanced, T2 weighted, Diffusion tensor imaging, MR spectroscopy, and Dynamic susceptibility contrast perfusion weighted (DSC-PWI) imaging.

Study Timeline

• Status Verified: 2020-03
• Study Start: 2020-03-15
• Study First Submitted: 2020-03-17
• Study First Submitted QC: 2020-03-17
• Study First Posted: 2020-03-19
• Last Update Submitted: 2020-03-20
• Last Update Posted: 2020-03-24
• Primary Completion: 2023-12-20
• Study Completion: 2024-06-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

• Age > 18
• Known or suspected recurrent malignant brain tumors
• Radiographic worsening reported on MRI shortly (within 3 months) after completion of radiation and temozolomide therapy
• Able to lie flat and/or still for a minimum of 60 minutes
• Willingness and ability to comply with scheduled visits and study procedures
• Patients who have a clinical indication for a PET-CT
• If female, patient must be postmenopausal or surgically sterile

Exclusion Criteria

• Conditions that preclude a clinical brain FDG PET study, including: Consumption of liquids with sugar and/or caffeine prior to the study, Blood glucose levels over 150 mg/mL, Eating or drinking calories of any type within 4 hours of radiotracer injection, Hyperinsulinemia, Patients who for any reason cannot tolerate lying supine for 60 minutes

• Conditions that preclude a FDOPA PET study, including: Consuming a diet that is NOT low in protein after the previous evening meal
• Tumor located in the striatum
• Changes in medication (new prescriptions or change in dosages) between visits 1 and 2
• Pregnant, nursing, or lactating
• Women of childbearing potential (premenopausal female capable of becoming pregnant), which also includes:

women on oral, injectable, or mechanical contraceptives, women who are single, women whose male partners have been vasectomized or whose male partners have received or are utilizing mechanical contraceptive devices

• Weight > 450 lbs
• Known allergic reactions to 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) and Fluorine-18 fluorodeoxyglucose (18F-FDG)
• Confirmation that study eligibility criteria have not been met between visits 1 and 2

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic	Multiparametric Magnetic Resonance Imaging Scan	Study subjects will receive 18FDG via an IV before undergoing one PET/CT scan over 60 minutes. They will then receive an IV injection of Gadovist for contrast before undergoing a multiparametric MRI scan. Subjects will also receive (18)F-FDOPA via an IV before undergoing another PET/CT scan over 60 minutes.
Diagnostic	Computed Tomography	Study subjects will receive 18FDG via an IV before undergoing one PET/CT scan over 60 minutes. They will then receive an IV injection of Gadovist for contrast before undergoing a multiparametric MRI scan. Subjects will also receive (18)F-FDOPA via an IV before undergoing another PET/CT scan over 60 minutes.
Diagnostic	fluorine F 18 fluorodopa	Study subjects will receive 18FDG via an IV before undergoing one PET/CT scan over 60 minutes. They will then receive an IV injection of Gadovist for contrast before undergoing a multiparametric MRI scan. Subjects will also receive (18)F-FDOPA via an IV before undergoing another PET/CT scan over 60 minutes.
Diagnostic	Positron Emission Tomography	Study subjects will receive 18FDG via an IV before undergoing one PET/CT scan over 60 minutes. They will then receive an IV injection of Gadovist for contrast before undergoing a multiparametric MRI scan. Subjects will also receive (18)F-FDOPA via an IV before undergoing another PET/CT scan over 60 minutes.
Diagnostic	Fludeoxyglucose F-18	Study subjects will receive 18FDG via an IV before undergoing one PET/CT scan over 60 minutes. They will then receive an IV injection of Gadovist for contrast before undergoing a multiparametric MRI scan. Subjects will also receive (18)F-FDOPA via an IV before undergoing another PET/CT scan over 60 minutes.

Primary Outcome Measures

Name	Time	Method
Quantitative parametric maps indicating differences in details (d) components of the wavelet transform analysis, d6 and d8, based on established tumor feature criterions.	Up to 6 months	Will be derived from MRI brain scan imaging.
Quantitative parametric maps indicating differences in rates of glucose and amino acid uptake (Ki) obtained from dynamic FDG and FDOPA scans respectively.	Up to 6 months	Will be derived from PET/CT scan imaging.
Semi-quantitative standardize uptake value (SUV) parametric maps based on static PET scans (last 20 minutes of the dynamic PET scans).	Up to 6 months	Will be derived from PET/CT scan imaging.
MRI brain metrics	Up to 6 months	Including anatomic assessment based on T1, T2, and contrast enhanced T1 weighted imaging, MR spectroscopy data (choline, creatinine, and N-acetyl acetate peak integrals and ratios), MR perfusion data (relative cerebral blood volume), and diffusion tensor imaging data (apparent diffusion coefficient, fractional anisotropy)
Surgical pathology or 3-6 month interval multidisciplinary clinical evaluation.	Up to 6 months	To be compared with the imaging analyses for comparing ability to differentiate tumor recurrence from radiation necrosis.

Trial Locations

Locations (1)

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States